tbuckley/cabot-search huggingface dataset:
Clinical characteristic and outcomes of <i>KRAS</i> G13 mutant non-small cell lung cancers.
Authors: Arun Muthiah, Rani Chudasama, Jennifer Mingrino, Adam J Olszewski, Habibe Kurt, Maria Garcia-Moliner, Hina Khan
Journal: Journal of Clinical Oncology (2022)

e21017 Background: KRAS is the most commonly mutated oncogene in lung adenocarcinoma. Different KRAS mutations (mts) have unique prognostic and therapeutic implications. New drugs to target KRAS G12C have raised interest in studying the unique clinical and molecular characteristics of the different KRAS subtypes. We sought to evaluate the clinical outcomes of KRAS G13C/D (*) mutant (mut) non-small cell lung cancers (NSCLC) patients (pts), compared to those with G12C and other non-G12C mutations. Methods: We identified 255 KRAS mt NSCLC pts at Brown University-Lifespan Cancer Institute that were diagnosed between 06/2016 to 12/2021. Demographics, therapies and outcomes were retrospectively recorded. Progression-free (PFS) and overall survival (OS) was compared using log-rank test. For clinical relevance, we divided pts into G12C, G13*, and other non-G12C groups. Treatments (tt) received were divided into chemotherapy alone and immune-checkpoint inhibitor (IO) containing regimens. Results: Across the KRAS cohort (n = 255), median age was 71 years and 62% were females. Most pts had advanced disease (85%) at diagnosis (dx) and &gt; 90% were smokers. Most common KRAS mt was G12C (42%), and 7% of pts had G13*. Compared to other KRAS mut groups, G13 * had worse PFS counted from dx (median 4 vs 12 m, p = .037). When comparing outcomes of any tt among pts with G13*, G12C and other non-G12C KRAS mut, G13 group had the worst PFS (2.1 vs 10.3 vs 6.4 m, p = .004) and OS (4.1 vs 27.8 vs 18.1 m, p = .027). When treated with IO-based regimens, pts with G13 had also worse outcomes than those with other KRAS mts: PFS 1.8 vs 7.3 m, respectively, (p &lt; 0.001) and OS 1.8 vs 16.5 m, respectively (p = .006). Within the G13 group, pts who received IO-based regimens had worse PFS (1.8 vs 7.9 m, p = .037) and OS (1.8 vs 16.1 m, p = .093), compared to chemotherapy alone. While response to all systemic therapies was poor in G13* group (disease control rate [DCR] 10%, p = .004), DCR was particularly low with IO-based tt in G13* (0%) compared to other groups (p = .023). Conclusions: Pts with KRAS G13C/D had poor survival and response to therapies in comparison with G12C and other non-G12C KRAS mts, particularly with IO-containing regimens. Recently (Judd et al, MCT-21-0201), STK11 and KEAP1 were reported to be frequently co-mutated with KRAS G13* (37.3 and 12.6%) compared to other KRAS mts, and this genotype may confer primary resistance to IO. We hypothesize that the poor outcomes and immune resistance in G13* mut may be secondary to higher prevalence of STK11 and KEAP1 co-mutations. Larger data sets should confirm our observations and correlate them with PD-L1 scores and co-mutations.[Table: see text]
Racial differences in interest and use of integrative medicine among patients with breast cancer.
Authors: Jori Sheade, Jincong Q. Freeman, Fangyuan Zhao, Olufunmilayo I. Olopade, Dezheng Huo, Rita Nanda
Journal: Journal of Clinical Oncology (2022)

12101 Background: Breast cancer treatment can be associated with side effects (SEs) that negatively impact quality of life. While some SEs can be treated with medications, such interventions come with additional SEs. Acupuncture, massage, meditation, music therapy and yoga have received ASCO endorsement for the management of therapy-related SEs. Many patients are interested in integrative services, but little is known about racial differences in interest and use of integrative services among patients with breast cancer. Methods: Breast cancer patients enrolled in the Chicago Multiethnic Epidemiologic Cohort study were sent a survey regarding their interest and use of five integrative services: acupuncture, massage, meditation, music therapy and yoga. Participants were asked how interested they would be in these services if offered, using a five-point Likert scale. Prior use was self-reported. Proportional odds were modeled for “interest” and binary logistic regression was modeled for “self-reported use.” Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were calculated, controlling for age, education, marital status, household income, insurance, Carlson comorbidity index, molecular subtype and stage. Results: 1,300 patients responded to the survey, 928 White and 285 Black. Compared with White patients in this cohort, Black patients were less educated, had a lower household income, were more likely enrolled in Medicaid/Medicare, and had a greater Carlson comorbidity index. Over 97% of patients had stage 0-III breast cancer. While there was no difference in interest in acupuncture between Black and White patients (aOR 1.1, 95% CI 0.8-1.7), Black patients were significantly more interested in the use of massage (aOR 1.9, 95% CI 1.3-2.8), meditation (aOR 2.0, 95% CI 1.4-3.0), music therapy (aOR 2.7, 95% CI 1.8-4.0) and yoga (aOR 2.1, 95% CI 1.4-3.1). Black patients were significantly less likely than Whites to report acupuncture use (aOR 0.5, 95% CI 0.3-0.8); but there were no racial differences in self-reported use of massage (aOR 0.8, 95% CI 0.5-1.3), meditation (aOR 0.8, 95% CI 0.5-1.4), music therapy (aOR 1.7, 95% CI 0.8-3.3) and yoga (aOR 0.7, 95% CI 0.4-1.2). Conclusions: Black patients with breast cancer expressed more interest in integrative services than their White counterparts; there were no racial differences in self-reported use of integrative services except an increased use of acupuncture among White patients. A breast program focused on equity should provide access to these resources for all patients. Interest and self-reported use of integrative services among patients with breast cancer, by race. [Table: see text]
LINC-07. Challenges in management of paediatric CNS tumors in low- and middle-income countries: experience from a tertiary center in Pakistan.
Authors: Nida Zia, Bushra Kaleem, Ahmer Hamid, Daniel Moreira
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: The cure rate of children with central nervous system (CNS) tumors in low- and middle-income countries (LMICs) is lower than high-income countries due to under diagnosis, treatment abandonment, lack of appropriate radiological, histopathologic, neurosurgical, radiotherapeutic, and pediatric oncologic services. The present study aimed to evaluate the treatment challenges observed in a tertiary center in Pakistan. MATERIALS AND METHODS: Patients younger than 17 years-of-age with CNS tumors either diagnosed at or referred to Indus Hospital from January 2015 to December 2021 were included. RESULTS: A total of 235 patients were included with a median age of 10.0 years and male preponderance (60.8%). The three most frequent CNS malignancies observed were glioma (105; 44.3%), medulloblastoma (63;26.6%), and ependymoma (34;14.3%). Of 235 patients, 45(19%) received palliative treatment upfront, 37(15.6%) were referred to other institutions for care, and 33 (13.9%) abandoned prior to treatment initiation. Of the 120 (51.0%) patients who started curative treatment, 74(61.6%) completed treatment, 22(18.3%) continue on treatment, 19(15.8%) abandoned treatment, and 5(4.2%) died during treatment . Overall survival in patients on curative treatment at the time of analysis was close to 80%. CONCLUSION: This study describes the outlook of care for children with CNS tumors in a tertiary center of Pakistan.It is observed that high rate of patients with upfront palliation and abandonment lead to poor outcomes. Stigma cancer, financial toxicity, delayed referral and burden of neurosurgeries in government sectors could be contributing to these outcomes. Further work must be done to clarify the barriers to quality care. Futhermore, a conscious effort to increase integrated care for these patients is of utmost importance.
LINC-05. Successful response to bevacizumab/irinotecan/temozolomide in a progressive choroid plexus carcinoma: A case report
Authors: Regina Navarro-Martin del Campo, Ivan Pozos-Ochoa, David Bañuelos-Gallo, Fernando Sanchez-Zubieta, Ana L Orozco-Alvarado
Journal: Neuro-Oncology (2022)

Abstract Choroid plexus carcinomas (CPC) are a rare type of aggressive pediatric brain tumors with poor survival rates, and no standard curative therapy after relapse. We report the case of a 1-year-oldmale, with a right lateral ventricular CPC and disseminated leptomeningeal disease. First line therapy was an initial surgery aborted due to hemorrhage and a second near total resection. After the second surgery six cycles of ICE regimen were applied. The MRI after primary therapy showed progression with a new lesion located on the optic pathway and leptomeningeal disease. At this point a second line therapy consisting of Bebacizumab 10 mg/kg and Irinotecan 125 mg/kg every 2 weeks and Temozolamide 150 mg/m2 every 4 weeks was given. He received up to 24 cycles. His imaging demonstrated 80% primary tumor reduction and improvement of leptomeningeal disease. This treatment gave him the time to turn 3 years old to receive 3D conformational craniospinal radiotherapy as follows: spine 24Gy, overdose 27 Gy to tumor bed and cranial for a total dose 51 Gy. The patient is now 19 months from the end of treatment with stable disease. He is clinically well, with good performance status (Lansky 100%) and attending school. The relevance to present this case is to highlight a safe and effective treatment for a relapsed CPC since there is not a curative therapy for these children.
Comparison of characteristics and outcomes of young onset versus average onset pancreatobiliary adenocarcinoma.
Authors: Thejus Jayakrishnan, Suneel Deepak Kamath, Kanika G. Nair, Wei Wei, Bassam N. Estfan, Smitha S. Krishnamurthi, Alok A. Khorana
Journal: Journal of Clinical Oncology (2022)

10522 Background: Young-onset gastrointestinal malignancies appear to be increasing in incidence but most investigations have focused on colorectal cancer and there are limited data on young-onset pancreatobiliary cancers (YO-PBA). We evaluated trends and characteristics of YO-PBA in comparison to average-onset disease (AO-PBA). Methods: The study cohort comprised patients with PBA (pancreatic adenocarcinoma, intra- and extra-hepatic cholangiocarcinoma) diagnosed between 2004 and 2017 from the National Cancer Database. YO-PBA was defined as diagnosis at age &lt; 50 years and AO-PBA as &gt;50 years. Logistic regression was used to assess factors associated with YO-PBA status, and cox proportional hazards modeling was performed to associate demographic and clinical factors with overall survival. Results: Of 360,764 patients analyzed, 20,822 (5.8%) were YO-PBA with a median age at diagnosis of 45 years (IQR 42 – 48) vs 70 (62-78) years for AO-PBA. The number of patients with YO-PBA increased by 33.3% during the study period compared to 111.8% for AO-PBA. Characteristics associated with YO-PBA were (p-values&lt;0.001 for all): male sex (6.3% YO-male out of all male patients vs 5.2% YO-female out of all female patients, OR 1.2), Black race (7.9% YO-Black vs 5.0% YO-White, OR 1.4), lower income (6.4% YO-lowest household income based category vs 5.5% highest, OR 1.3), and lower education (6.9% YO-lowest educational status category vs. 4.9% highest, OR 1.4). YO-PBA were more likely to present with stage-IV disease (6.4% YO-Stage IV of all stage IV vs 5.4% YO-Stage I-III, OR 1.2, p-value&lt;0.0001), but more likely to undergo surgery (7.4% YO-surgery patients vs 5.4% YO no-surgery patients). Median OS was YO 11.0 (95% CI 10.8 – 11.3) vs. AO 7.1 months (95% CI 7.0 – 7.1). Effects of patients’ characteristics on OS differed significantly between YO and AO-PBA cohorts (interaction p-values &lt; 0.001), and were analyzed separately (table). Notably, Black patients experienced worse outcomes in both age groups. Conclusions: Young-onset pancreatobiliary cancers (YO-PBA) reported in NCDB have increased over the years. YO-PBA is associated with better survival compared to AO-PBA. Socioeconomic disparities significantly impact incidence and outcomes. More work is needed to help address these health disparities, especially for those with young-onset cancer. [Table: see text]
Gender disparities in multiple myeloma publications.
Authors: Aala Dweik, Hadeel Dweik, Hira Mian, Meera Mohan, Carolina D. Schinke, Samer Al Hadidi
Journal: Journal of Clinical Oncology (2022)

e23000 Background: Gender disparities exist in academia and are disproportionately affecting females. We conducted a cross sectional study to analyze gender disparities in MM publications in high impact hematology/oncology journals between January 1 st , 2016 and December 31 st , 2020. Methods: Data was collected through Medline/PubMed database search. High impact journals (impact factor &gt; 10) with at least ten MM related publications were included. Impact factor data was based on the 2016 InCites Journal Citation Report. We used Genderize, a validated database, to determine authors’ gender. Search engines were used if gender was undetermined or did not meet a cut-off of 0.9. Unclassified genders after search were excluded from analysis. Results: A total of 679 publications with 8898 authorships were analyzed. Mean number of authors for females vs. males, per publication was 4.4 and 8.7, respectively. Females constituted a third of total authors. Female first authors, corresponding authors and last/senior authors were 34%, 21% and 18%, respectively. 17% of authors of clinical trial publications were females. Publications by country had comparable percentages (30% females as first authors in the U.S. vs. 32% females as first authors in other countries). The proportion of female authorship in 2020 when compared to 2016 was similar (33%). Between 2016 and 2020, there was slight improvement in female first authors (32%-37%), last authors (16%-21%), and corresponding authors (17%-22%). Conclusions: Gender disparities in MM publications exist and are more obvious in the last/corresponding authorship in both the U.S. and other countries. Despite improvement in proportion of female authors, it remains suboptimal when compared to the growing proportion of female physicians. Efforts should be made to identify factors that contribute to these disparities and work to resolve them.
The genetic landscape of germline<i>DDX41</i>variants predisposing to myeloid neoplasms
Authors: Peng Li, Sara Brown, Margaret Williams, Thomas White, Wei Xie, Wei Cui, Deniz Peker, Li Lei, Christian A. Kunder, Huan-You Wang, Sarah S. Murray, Jennie Vagher, Tibor Kovacsovics, Jay L. Patel
Journal: Blood (2022)
A more extended pelvic lymph node dissection decreases recurrence rates in selected prostate cancer patients undergoing radical prostatectomy
Authors: G. Gandaglia, G. Rosiello, F. Pellegrino, A. Pellegrino, M. Bandini, A. Salonia, M. Tutolo, M. De Angelis, G. Sorce, A. Stabile, E. Mazzone, V. Cucchiara, E. Zaffuto, V. Mirone, P. Karakiewicz, S. Shariat, F. Montorsi, A. Briganti
Journal: European Urology (2022)
Finite Element Modeling of Pulmonary Mechanics in Severe Acute Respiratory Distress Syndrome: Explaining the Inclination Angle?
Authors: Eline Oppersma, Stijn Geraats, Nicolien H. Heikens, Arjen Welleweerd, Chiel A. Woerts, Libera Fresiello, Christiaan L. Meuwese, Dirk W. Donker
Journal: American Journal of Respiratory and Critical Care Medicine (2022)
Comparison of clinical pathological features, surgical treatments and prognosis of Gallbladder Neuroendocrine Neoplasms between Chinese and American population: Based on a nationwide multicenter study and SEER database.
Authors: Xuheng Sun, Yingbin Liu, Yijun WANG
Journal: Journal of Clinical Oncology (2022)

e16119 Background: Gallbladder Neuroendocrine Neoplasm (GB-NEN) is an extremely rare type of gallbladder neoplasms and its characteristics and prognosis varies widely. The focus of this study was to analyze and compare the clinical pathological features, surgical treatments and prognosis of patients with GB-NEN between Chinese and American population. Methods: The Chinese Research Group of Gallbladder Cancer (CRGGC) study is a multicenter retrospective registry cohort study reviewing the electronic medical records from 76 tertiary and secondary hospitals across 28 provinces in China. Patients diagnosed with GB-NEN according to the 2019 WHO classification between 2010 and 2017 were assembled from CRGGC study and National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. Chi-square test for categorical variables and the overall survival outcomes were analyzed by the Kaplan–Meier method in the two groups before and after a propensity score matching (PSM) with 1:1 ratio. Results: In this study, we assembled totally 84 patients from CRGGC study and there were 217 patients with GB-NEN diagnosed during the same period from National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) database. After the PSM using sex, age, American Joint Committee on Cancer stage 7 th Edition, liver invasion status and types of surgical treatment, 19 pairs of patients were included. Chinese patients from the CRGGC with GB-NENs presents more liver invasion (c²= 22.621, P = 0.000), higher diagnosed age (c²= 37.313, P = 0.000) and cancer stage (c²= 13.298, P = 0.021) totally than those from the SEER database. Radical surgical treatments were performed in 51(60.714%) and 96(44.240%) patients among patients from the CRGGC study and the SEER database respectively and the surgical treatment model shows a difference between these two groups (c²= 85.729, P = 0.000). Compared with propensity score matched American patients with GB-NENs from SEER database, Chinese patients from the CRGGC study had similar overall survival(c²= 0.480, P = 0.489) instead of longer overall survival than patients from the SEER database before PSM(c²= 6.408, P = 0.011). Conclusions: Chinese and American patients with GB-NEN form the CRGGC study and the SEER database present no difference in overall survival after PSM. However, heterogeneity of pathological features, surgical treatments between those groups of GB-NEN patients prompt that different methods could be referred for the improvement in the survival of GB-NEN patients.
How to regulate vaping products to advance cancer prevention: Evidence from online stores.
Authors: Ce Shang
Journal: Journal of Clinical Oncology (2022)

e22502 Background: The use of electronic cigarettes has significantly increased in the past decade, and online stores are one of the most common outlets for e-cigarette users to purchase vaping products. The goal of this study is to examine the appeal of different e-liquid flavors to vapers, using a revealed preference method to estimate consumer demand. Methods: We collected data on e-liquid sales prices, volume (in ml), and a variety of product flavors, from online vaping stores using web data extraction. We standardized prices for e-liquid products and used the hedonic pricing model to assess the associations between standardized e-liquid prices and flavors, controlling for nicotine concentration (in mg) and product VG/PG ratio. In total, we collected data of 10,870 e-liquid products from four popular online vaping stores that sell nationwide across the U.S. Results: Higher e-liquid prices (standardized to $/ml) are associated with higher nicotine concentrations. E-liquid products with fruit tobacco flavors are associated with higher sales prices. E-liquid prices are higher when VG/PG ratio deviates from 70/30 except for 90/10: the prices of e-liquid products with a 90/10 VG/PG ratio are lower than the prices of products with a 70/30 ratio. All of the findings above are statistically significant at a 5% level. Conclusions: Higher nicotine concentration and fruit flavors are associated with higher e-liquid prices in national online vaping stores, suggesting that they are preferred attributes and are in greater demand among vapers in the market of heterogeneous e-liquid products.
MEDB-63. Deciphering the role of LIN28B in Group 3 medulloblastoma
Authors: Shubin Shahab, Jessica Sun, Robert Schnepp, Tobey MacDonald, Anna Kenney
Journal: Neuro-Oncology (2022)

Abstract BACKGROUND: Children with Group 3 medulloblastoma (MB) have a very poor long-term outcome and many do not survive beyond 5 years. Several drivers for Group 3 MB have been identified but none have resulted in targeted therapy to date. LIN28B is a stem cell factor that is upregulated in Group 3 medulloblastoma and is associated with worse survival. Here we investigate the role of the LIN28B pathway in Group 3 MB development. Pharmacologic inhibition of the LIN28B pathway is feasible and may provide a unique opportunity to target this tumor. METHODS: Using LIN28B knockdown and overexpression in G3 MB cells we test LIN28B’s effect on proliferation, self-renewal and metastasis. Similarly, we used shRNAs targeting PBK and demonstrate a similar effect on G3 MB growth. We also investigate the role of let-7 as a target of LIN28B by introducing let-7 mimetics and overexpression vectors into MB cells. Finally, we use a LIN28 inhibitor 1632 and a PBK inhibitor HITOPK032 to treat G3 MB cell lines and then assess their impact on proliferation and apoptosis. RESULTS: We find that down-regulation of LIN28B or PBK using shRNA results in significant reduction in cell proliferation. In contrast overexpression of LIN28B increases Group 3 cell proliferation and tumor sphere formation. LIN28B knockdown also significantly (p&amp;lt; 0.01) increases survival in mice with orthotopic Group 3 tumors. The LIN28 inhibitor 1632 also leads to significant reduction in G3 MB growth through decreased cell cycle entry and increased apoptosis. In addition, HITOPK032 also demonstrates significant reduction in Group 3 MB cell proliferation at low (nanomolar to low micromolar) concentration. CONCLUSIONS: Our study establishes a critical role for the LIN28B-let-7-PBK pathway in Group3 MB and provides encouraging preliminary preclinical results for drugs that target this pathway.
Are phenome-wide association studies feasible in a developing country?
Authors: Gerard G. Dumancas, Destiny Harrison, Jonathan Adam Rico, Pia Regina Fatima C. Zamora, Aretha G. Liwag, Joselito F. Villaruz, Ma. Luz Vicenta V. Guanzon, Hans Francis D. Ferraris, Patrick Joseph B. Jalandoni, Webster F. Padernal, Bea Nestie L. Villareal, Ria A. Maculada, Rachael Mae A. Fernandez, Felix Ray Villa, Romulo de Castro
Journal: Trends in Genetics (2022)